BACKGROUND: Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor. METHODS: The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary. RESULTS: In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites. CONCLUSIONS: Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.
BACKGROUND: Central nervous system involvement is a well recognized complication of systemic non-Hodgkin lymphoma. Most central nervous system recurrences occur within the first 2 years after the initial diagnosis and are considered to represent clonally related recurrence of systemic disease. The authors attempted to investigate the clonal relation between the late-delayed central nervous system involvement and the original systemic tumor. METHODS: The authors studied archival, formalin fixed, paraffin embedded tissue samples from 8 patients with isolated cerebral involvement diagnosed > 3 years after their initial presentation with aggressive, systemic, B-cell non-Hodgkin lymphoma. The rearranged immunoglobulin heavy-chain variable region genes (VH) from both sites were amplified by polymerase chain reaction and were sequenced when necessary. RESULTS: In three of five patients who had interpretable results, a distinct, monoclonal, VH family-specific band profile was obtained from the cerebral and systemic lymphoma. In the other two patients, a similar VH band pattern was observed and also was compared using direct sequencing, which demonstrated sequence differences between tumors from the two sites. CONCLUSIONS: Clonal variance between the cerebral and systemic lymphoma in these patients suggested the possibility that some instances of late-delayed recurrence in the central nervous system represent a second, new B-cell lymphoma rather than a true recurrence of the original systemic tumor, a finding that may have significant clinical and biologic implications.
Authors: D Juskevicius; T Lorber; J Gsponer; V Perrina; C Ruiz; F Stenner-Liewen; S Dirnhofer; A Tzankov Journal: Leukemia Date: 2016-05-20 Impact factor: 11.528